Freeze-fracture electron microscopy has been used to demonstrate that vasopressin (ADH) stimulation of the isolated toad urinary bladder is accompanied by an alteration in granular cell luminal membrane structure which quantitatively and specifically relates to hormonally-induced increments in bladder osmotic water permeability. This alteration consists of the organized aggregation of intramembranous particles and occurs at multiple membrane sites. In extension of our previous efforts with toad bladder, we plan to study the possible functional roles of microtubules, microfilaments, and secretory granules in the aggregation response to ADH as well as whether aggregates themselves are structurally consistent with the hypothesis that they are sites for transmembrane water passage. With use of the same preparation (toad bladder), we plan also to follow-up on recent observations of distinctive elongated particles in the luminal membrane of some, but not all, mitochondria-rich cells by determining whether the presence of these particles and/or their arrangement are altered in association with either ADH or aldosterone stimulation. Finally, we have recently established that intramembranous particles in papillary collecting duct cell luminal membrane for Brattleboro rats with hereditary diabetes insipidus aggregate in response to ADH. Our planned experiments with these animals include confirming the apparent physiologic significance of this structural response and defining whether it involves the addition of new material into the membrane or a rearrangement of material already there.